정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

변연성 발육성 치아종 : A Case of Peripheral Developing Odontoma

윤정훈,임경수,손홍범 조선대학교 구강생물학연구소 2003 Oral Biology Research (Oral Biol Res) Vol.27 No.1

A peripheral odontoma is a relatively rare lesion and is thought to represent the soft tissue counterpart of the central or intraosseous odontoma. Although several odontogenic tumors can occur peripherally, only a few cases of peripheral odontomas involving the gingival tissues have been reported. No earlier stage of peripheral odontoma or peripheral developing odontoma has been described. Here, we report a case of a peripheral developing odontoma occurring in the gingiva of a 4-rear-old Korean boy. Microscopic sections showed several nodules of developing rudimentary tooth germ-like structures in the gingival tissue. It seems likely that this case arise from remnants of the dental lamina located in the gingiva, since the clinical and histologic presentation lends support to the peripheral origin of this tumor.

가족성 고콜레스테롤혈증 유병자에서 HMG Co-A Reductasen Inhibitor 및 Bile Acid Resin의 투여로 인한 아킬레스건 황색종의 감소

채인호,한기훈,박영배,조주희,김효수,손대원,김철호,오병희,이명묵,최윤식,서정돈,이영우 대한순환기학회 1997 Korean Circulation Journal Vol.27 No.9

골반내에 발생한 Proximal-type 유상피성 육종 1예

길준철,이상수,전병화,김성훈,손우석,목정은,박양순,강길현 대한부인종양 콜포스코피학회 2003 Journal of Gynecologic Oncology Vol.14 No.4

유상피성 육종은 매우 드문 악성 연조직 육종으로, 전형적인 경우들은 주로 젊은 남성의 수부, 전완부와 같은 신체의 원위부에 피하 혹은 심재성 피부 종괴로 발생하며, 조직학적 소견상 적은 비정형성을 나타내는 유상피성 세포와 방추형 세포의 증식에 의한 다발성 결절 형태의 배열을 보인다. 최근에 전형적인 유상피성 육종과 조직학적 유사성을 가지나 더 공격적인 형태인 proximal-type 유상피성 육종이 보고되었으며, proximal-type은 전형적인 유상피성 육종에 비하여 현저한 유상피성 세포의 발현과 매우 심한 비정형성을 나타내며, 세포가 매우 크고, 소포성 핵과 뚜렷한 핵소체를 보이며, 자주 rhabdoid 세포의 양상을 띈다. 임상적으로는 전형적인 형태에 비하여 호발 연령이 조금 늦고, 주로 체간부에, 특히 골반, 회음부, 생식기 등과 같은 심부에 발생하고, 더욱 공격적인 양상을 나타낸다. 저자들은 13세 소녀에서 원발부위를 알 수 없는, 골반내에 발생한 proximal-type 유상피성 육종 1예를 경험하여, 문헌 고찰과 함께 보고하는 바이다. Epithelioid sarcoma is a rare malignant soft-tissue sarcoma with an unknown histiogenesis, typically presenting as a subcutaneous or deep dermal mass lesion in the distal portions of the extremities of young adults. Recently, a more aggressive, so-called 'proximal-type' epithelioid sarcoma has been reported. In contrast to conventional epithelioid sarcoma, the proximal type is characterized by a predominantly large cell epithelioid cytomorphology, marked cytologic atypia, and frequent occurrence of rhabdoid features in most patients. Proximal-type epithelioid sarcoma has a predilection for appearing in the genitalia, especially the vulva, penis, pelvis and buttocks. Also this lesion appears to be somewhat more aggressive or at least metastasizes earlier than the conventional epithelioid sarcoma. We report a 13-year-old girl who presented with a buge mass filling the pelvic cavity which was painful, hard and fixed on palpation, and was radiologically diagnosed as a malignant germ cell tumors on the CT scan. The mass was surgically excised and pathologically proved to be an proximal-type epithelioid sarcoma of unknown origin.

HETEROLOGOUS GENE EXPRESSION AND SECRETION OF THE ANTICOAGULANT HIRUDIN IN A METHYLOTROPHIC YEAST HANSENULA POLYMORPHA

Jung Hoon Sohn,Michael Yu Beburov,Eui Sung Choi,Sang Ki Rhee 생화학분자생물학회 1993 생화학분자생물학회 춘계학술발표논문집 Vol.- No.-

Yeast Engineering towards Consolidated Bioprocessing for Cost-effective Production of Cellulosic Bioethanol

Jung-Hoon SOHN 한국생물공학회 2011 한국생물공학회 학술대회 Vol.2011 No.4

유전자 재조합에 의해 제조된 하루딘의 항응고 작용

정기화,김영식,이상기,손정훈,최의성,엄은미,정정숙,정춘식 한국응용약물학회 1993 Biomolecules & Therapeutics(구 응용약물학회지) Vol.1 No.2

Hirudin is a potent inhibitor of thrombin, which was originally obtained from the medicinal leech (Hirudo medicinalis). Now it is being produced through the recombinant technology on a large scale. Recombinant hirudin has been assayed for the anticoagulant activity by the measurement of clotting time and the inhibition of thrombin actvity using a chromogenic substrate. The assay range of partial thromboplastin time and thrombin time is within 0.2∼1.0 ,㎍/㎖. Thrombin time is more sensitive to the measurement of clot. Ex vivo study showed the level of hirudin in rat plasma was highest in 10 min and then it was eliminated slowly. The half-life of r-hirudin was 80∼110 min depending on the assay methods. Intraveneous injection of russel viper venom was used for thrombus induction combined with vena cava ligation. Inhibition of venous thrombosis was observed with i.v. hirudin. It was dependent on the concentration of hirudin.

Apoptosis Induced by Tanshinone IIA and Cryptotanshinone Is Mediated by Distinct JAK/STAT3/5 and SHP1/2 Signaling in Chronic Myeloid Leukemia K562 Cells

Jung, Ji Hoon,Kwon, Tae-Rin,Jeong, Soo-Jin,Kim, Eun-Ok,Sohn, Eun Jung,Yun, Miyong,Kim, Sung-Hoon Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>Though tanshinone IIA and cryptotanshinone possess a variety of biological effects such as anti-inflammatory, antioxidative, antimetabolic, and anticancer effects, the precise molecular targets or pathways responsible for anticancer activities of tanshinone IIA and cryptotanshinone in chronic myeloid leukemia (CML) still remain unclear. In the present study, we investigated the effect of tanshinone IIA and cryptotanshinone on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. We found that both tanshinone IIA and cryptotanshinone induced apoptosis by activation of caspase-9/3 and Sub-G1 accumulation in K562 cells. However, they have the distinct JAK/STAT pathway, in which tanshinone IIA inhibits JAK2/STAT5 signaling, whereas cryptotanshinone targets the JAK2/STAT3. In addition, tanshinone IIA enhanced the expression of both SHP-1 and -2, while cryptotanshinone regulated the expression of only SHP-1. Both tanshinone IIA and cryptotanshinone attenuated the expression of bcl-x<SUB>L</SUB>, survivin, and cyclin D1. Furthermore, tanshinone IIA augmented synergy with imatinib, a CML chemotherapeutic drug, better than cryptotanshinone in K562 cells. Overall, our findings suggest that the anticancer activity of tanshinone IIA and cryptotanshinone is mediated by the distinct the JAK/STAT3/5 and SHP1/2 signaling, and tanshinone IIA has the potential for combination therapy with imatinib in K562 CML cells. </P>

Melatonin Suppresses the Expression of 45S Preribosomal RNA and Upstream Binding Factor and Enhances the Antitumor Activity of Puromycin in MDA-MB-231 Breast Cancer Cells

Jung, Ji Hoon,Sohn, Eun Jung,Shin, Eun Ah,Lee, Duckgue,Kim, Bonglee,Jung, Deok-Beom,Kim, Ji-Hyun,Yun, Miyong,Lee, Hyo-Jeong,Park, Yong Koo,Kim, Sung-Hoon Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>Since the dysregulation of ribosome biogenesis is closely associated with tumor progression, in the current study, the critical role of ribosome biogenesis related signaling was investigated in melatonin and/or puromycin induced apoptosis in MDA-MB-231 breast cancer cells. Despite its weak cytotoxicity, melatonin from 3 mM attenuated the expression of 45S pre-ribosomal RNA (pre-rRNA), UBF as a nucleolar transcription factor, and fibrillarin at mRNA level and consistently downregulated nucleolar proteins such as UBF and fibrillarin at protein level in MDA-MB-231 cells. Furthermore, immunofluorescence assay revealed that UBF was also degraded by melatonin in MDA-MB-231 cells. In contrast, melatonin attenuated the expression of survival genes such as Bcl-xL, Mcl-1, cyclinD1, and cyclin E, suppressed the phosphorylation of AKT, mTOR, and STAT3, and cleaved PARP and activated caspase 3 only at a high concentration of 12 mM. However, combined treatment of melatonin (3 mM) and puromycin (1 <I>μ</I>M) synergistically inhibited viability, attenuated the expression of 45S pre-rRNA and UBF, and consistently downregulated UBF, XPO1 and IPO7, procaspase 3, and Bcl-xL in MDA-MB 231 cells. Overall, these findings suggest that melatonin can be a cancer preventive agent by combination with puromycin via the inhibition of 45S pre-rRNA and UBF in MDA-MB 231 breast cancer cells.</P>

CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells

Sohn, Eun Jung,Jung, Deok-Beom,Lee, HyoJung,Han, Ihn,Lee, Jihyun,Lee, Hyemin,Kim, Sung-Hoon Elsevier 2018 Cancer letters Vol.412 No.-

<P><B>Abstract</B></P> <P>Here the underlying role of CNOT2, a subunit of CCR4-NOT complex, was elucidated in cancer progression. CNOT2 was overexpressed in HIT-T15, ASPC-1, BXPC-3, PC-3, LNCaP, MCF-7 and MDA-MB-231 cell lines, which was confirmed by Tissue array in various human tumor tissues. Also, CNOT2 depletion suppressed proliferation and colony formation of MDA-MB-231 cells. Of note, microarray revealed decreased expression of CNOT2, VEGF-A, HIF2 alpha (<0.5 fold) and increased expression of UMOD1, LOC727847, MMP4, hCG and other genes (>2.0 fold) in CNOT2 depleted MDA-MB-231 cells compared to untreated control. Consistently, downregulation of VEGF, CNOT2 and HIF2 alpha was verified in CNOT2 depleted MDA-MB-231 cells by RT-qPCR. Additionally, CNOT2 depletion inhibited VEGF induced tube formation in HUVECs and reduced neovascularization in CAM assay. Furthermore, the growth of CNOT2 depleted MDA-MB-231 cells was significantly reduced in Balb/c nude mice along with decreased expression of VEGF and PCNA by immunohistochemistry compared to untreated control group. Overall, our findings provide evidences that CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells as a potent molecular target for breast cancer treatment.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CNOT2 was overexpressed in HIT-T15, ASPC-1, BXPC-3, PC-3, LNCaP, MCF-7 and MDA-MB-231 cell lines compared to normal cells. </LI> <LI> CNOT2 depletion suppressed proliferation and colony formation of MDA-MB-231 cells. </LI> <LI> CNOT2 depletion inhibited VEGF induced tube formation in HUVECs and reduced neovascularization in CAM assay. </LI> <LI> CNOT2 depletion suppressed the growth of MDA-MB-231 cells in Balb/c nude mice along with decreased expression of VEGF and PCNA by IHC. </LI> <LI> Overall, CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells. </LI> </UL> </P>